Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling

In the outer plexiform layer (OPL) of the mouse retina, two types of cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). This transmission is modulated by a single horizontal cell (HC) type, the only interneuron in the outer retina. Horizontal cells form feedback synapses with cones and feedforward synapses with CBCs. However, the exact computational role of HCs is still debated. Along with performing global signaling within their laterally coupled network, HCs also provide local, cone-specific feedback. Specifically, it has not been clear which synaptic structures HCs use to provide local feedback to cones and global forward signaling to CBCs. Here, we reconstructed in a serial block-face electron microscopy volume the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites to quantitatively analyze their connectivity. In addition to the fine HC dendritic tips invaginating cone axon terminals, we also identified “bulbs”, short segments of increased dendritic diameter on the primary dendrites of HCs. These bulbs are located well below the cone axon terminal base and make contact to other cells mostly identified as other HCs or CBCs. Using immunolabeling we show that HC bulbs express vesicular gamma-aminobutyric acid transporters and co-localize with GABA receptor γ2 subunits. Together, this suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysics-based computational model of a HC dendritic branch supports the hypothesis that the spatial arrangement of synaptic contacts allows simultaneous local feedback and global feedforward signaling

Individual and integrated methods on tough lovegrass control.

ABSTRACT: The current study evaluated the efficiency of mechanical, physical, chemical and cultural methods, used exclusively or integrated, to control tough lovegrass. The experimental design was completely randomized, with 15 treatments and four repetitions. Physical control of tough lovegrass was based on the application of fire, whereas mechanical controls consisted in mowing and harrowing/plowing procedures. The herbicide clethodim and different glyphosate salts were evaluated for chemical control. Glyphosate and soil fertility correction were applied as cultural and integrated methods, in addition to isopropylamine + potassium salts combination, soil fertility correction and implantation of one of the following forage plants: Elephant grass, Pangola grass, Forage peanut and Birdsfoot trefoil. The effect of treatments on the incidence of tough lovegrass and on its botanical composition was evaluated one year after their applications. Isolated control methods, except for glyphosate using, did not present efficient tough lovegrass control. Glyphosate salts could control tough lovegrass plants, but their association with improved soil fertility and Pangola grass implantation was the best strategy to control the invasive plant. Key words: Eragrostis plana Nees, native pasture, weed control

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4-Induced Fibrosis

BACKGROUND: Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. HYPOTHESIS AND AIMS: We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. ANIMALS AND METHODS: Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. RESULTS: Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. CONCLUSIONS: Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers